(a) Field
The invention relates generally to novel chemical compounds and methods. More particularly, the invention provides novel spirocyclic molecules, having protein tyrosine kinase inhibitory activity, and methods of synthesizing and using such compounds. Preferred compounds are c-Met and/or ALK inhibitors useful for the treatment of abnormal cell growth, such as cancers.
(b) Related Prior Art
The protein kinases represent a large family of proteins which play a central role in the regulation of a wide variety of cellular processes and maintain control over cellular function. A partial, non limiting, list of such kinases includes ALK, abl, Akt, bcr-abl, Blk, Brk, c-kit, c-met, c-src, CDKI, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDKIO, bRaf, cRafl, CSK, EGFR, ErbB2, ErbB3, ErbB4, Erk, Pak, fes, FGFRI, FGFR2, FGFR3, FGFR4, FGFR5, Fgr, flt-1, flt-3, Fps, Frk, Fyn, Hck, IGF-IR, INS-R, Jakl, Jak2, Jak3, KDR, Lck, Lyn, FAK, MEK, p38, PDGFR, PDC, PKC, PYK2, ros, tie, tie2, Pim-1, P13k, TRK and Zap70. Abnormal protein kinase activity has been related to several disorders, ranging from non-life threatening diseases such as psoriasis to extremely serious diseases such as cancers.
This invention concerns a new family of novel spirocyclic compounds that are c-Met and/or ALK inhibitors and their use in treating cancers and other diseases. Unexpectedly, the novel spirocyclic compounds of the present invention exhibit improved inhibitory activity against ALK mutant enzymes that are more resistant to Crizotinib, therefore may provide a more effective treatment for diseases caused by abnormality of ALK enzyme.